The dopamine D3 receptor subtype is a member of the dopamine D2 subclass of receptors. These receptors have been implicated in a number of central nervous system (CNS) disorders including but not limited to psychostimulant abuse, psychosis and Parkinson's disease (Le Foll et al., Eur J Psychiatry 15:140-146 (2000); Joyce, Pharmacol Ther 90(2-3):231-259 (2001)). Compounds that bind with high affinity and selectivity to D3 receptors can not only provide important tools with which to study the structure and function of this receptor subtype, but may also have therapeutic implications in these psychiatric and neurologic disorders.
Ger. Offen. DE 4,425,144 (equivalent to U.S. Pat. No. 6,124,294) discloses triazole compounds and their use for treating disorders which respond to dopamine D3 ligands. U.S. Pat. No. '294 fails to disclose any compounds that do not include a triazole ring. Thus all of the compounds of U.S. Pat. No. '294 are outside the scope of the present invention. Ger. Offen. DE 4,425,143 (equivalent to U.S. Pat. No. 6,342,604) discloses pyrimidine compounds and their use for treating disorders which respond to dopamine D3 ligands. U.S. Pat. No. '604 fails to disclose any compounds that do not include a thioether linkage. Thus all of the compounds of U.S. Pat. No. '604 are outside the scope of the present invention. Finally, Ger. Offen. DE 4,425,145 (equivalent to U.S. Pat. No. 5,958,923) discloses thiazole compounds and their use for treating disorders which respond to dopamine D3 ligands. U.S. Pat. No. '923 fails to disclose any compounds that do not include a thiazole ring. Thus, all of the compounds of U.S. Pat. No. '923 are considered to fall outside the scope of the present invention.
The compounds of the invention are useful as imaging agents (PET, SPECT) for D3 receptors in the central nervous system and have utility in diagnosis of disease states related to abnormal D3 receptor function or expression. Structurally rigid analogs provide selective and orally bioavailable drugs that are superior to currently available D3 receptor ligands. These compounds have therapeutic use in treating substance abuse, especially cocaine and amphetamine, psychosis, and Parkinson's disease.